The compound 5-({[(2S)-2-amino-3-(4-carbamoyl-2,6-dimethylphenyl)propionyl]-[(1S)-1-(4-phenyl-1H-imidazol-2-yl)ethyl]amino}-methyl)-2-methoxybenzoic acid, commonly known as Eluxadoline, is described in WO 2003/092688 A2. Eluxadoline is an opioid receptor modulator, and is marketed in the United States as VIBERZI® for the treatment of irritable bowel syndrome with diarrhea (IBS-D).

Crystalline forms of Eluxadoline, including hydrated and solvated forms, are reported, for example, in WO 2009/009480 A2, WO 2017/015606 A1 and WO 2017/114446 A1. However, these reported crystalline forms are associated with various problems, such as hygroscopicity, tendency to desolvation/dehydration during drying procedures or upon exposure to low humidity conditions; poor characterization leading to questions of controllability and reproducibility, the incorporation or use of solvents classified as toxic according to established ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines such as Q3C(R6), or preparations that are impractical for commercial use. The tendency of forms to desolvate/dehydrate limits their usefulness in commercial products since it requires specialised practices to avoid desolvation/dehydration during drying, handling, storage and formulation activities. Furthermore, the variable and/or undefined nature of some of these forms has regulatory implications, as the characteristics of an active pharmaceutical ingredient must be well-defined and controlled.
Different crystalline forms of the same compound may have different packing, thermodynamic, spectroscopic, kinetic, surface and mechanical properties. For example, different crystalline forms may have different stability properties. A particular crystalline form may be more sensitive to heat, relative humidity (RH) and/or light. Alternatively or additionally, a particular crystalline form may provide more compressibility and/or density properties thereby providing more desirable characteristics for formulation and/or product manufacturing. Particular crystalline forms may also have different dissolution rates, thereby providing different pharmacokinetic parameters, which allow for specific forms to be used in order to achieve specific pharmacokinetic targets. Additionally, the particular solubility characteristics of a given crystalline form in relation to undesired impurities can result in differences in the chemical purity of different crystalline forms upon isolation. Differences in stability may result from changes in chemical reactivity, such as differential oxidation. Such properties may provide for more suitable product qualities, such as a dosage form that is more resistant to discolouration when comprised of a specific crystalline form. Different physical properties of crystalline forms may also affect their processing. For example, a particular crystalline form may be more resistant to flow, or may be more difficult to filter and/or wash.
Although general approaches to crystalline form screening of active pharmaceutical ingredients are known, it is well established that the prediction of how a given compound will crystallize is not possible. Furthermore, prediction of the properties of any unknown crystalline forms, and how they will differ from other crystalline forms of the same compound, remains even more elusive (Joel Bernstein, Polymorphism in Molecular Crystals, Oxford University Press, New York, 2002, page 9).
Therefore, there exists a need for novel crystalline forms of Eluxadoline for use in providing improved drug products containing Eluxadoline and their manufacture.